Influence of immunosuppressive treatment on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation.

This study was conducted to elucidate the influence of immunosuppressive treatment (IST) and GVHD on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation (HCT). The study cohort included 2656 patients who received allogeneic HCT after high-intensity conditioning regimens for treatment of hematologic malignancies. Rates and hazard ratios of relapse and mortality were analyzed according to GVHD and IST as time-varying covariates. Adjusted Cox analyses showed that acute and chronic GVHD were both associated with statistically similar reductions in risk of relapse beyond 18 months after HCT but not during the first 18 months. In patients with GVHD, resolution of GVHD followed by withdrawal of IST was not associated with a subsequent increase in risk of relapse. In patients without GVHD, withdrawal of IST was associated with a reduced risk of relapse during the first 18 months, but the risk of subsequent relapse remained considerably higher than in patients with GVHD. In summary, the association of GVHD with risk of relapse changes over time after HCT. In patients without GVHD, early withdrawal of IST might help to prevent relapse during the first 18 months, but other interventions would be needed to prevent relapse at later time points.

[1]  Michael Boeckh,et al.  Reduced mortality after allogeneic hematopoietic-cell transplantation. , 2010, The New England journal of medicine.

[2]  Y. Kodera,et al.  Impact on relapse of corticosteroid therapy after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia , 2010, Clinical transplantation.

[3]  R. Porcher,et al.  The graft-versus-leukemia effect is mainly restricted to NIH-defined chronic graft-versus-host disease after reduced intensity conditioning before allogeneic stem cell transplantation , 2010, Leukemia.

[4]  M. Mohty,et al.  NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: report from the Committee on the Epidemiology and Natural History of Relapse following Allogeneic Cell Transplantation. , 2010, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[5]  N. Kröger,et al.  Introduction to the reports from the National Cancer Institute First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation. , 2010, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[6]  J. Ritz,et al.  NCI First International Workshop on The Biology, Prevention, and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on the Biology Underlying Recurrence of Malignant Disease following Allogeneic HSCT: Graft-versus-Tumor/Leukemia Reaction. , 2010, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[7]  R. Storb,et al.  Life expectancy in patients surviving more than 5 years after hematopoietic cell transplantation. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  R. Jenq,et al.  Relapse after allogeneic hematopoietic cell therapy. , 2010, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[9]  B. Storer,et al.  Evaluation of NIH consensus criteria for classification of late acute and chronic GVHD. , 2009, Blood.

[10]  J. Fay,et al.  Evaluation of mycophenolate mofetil for initial treatment of chronic graft-versus-host disease. , 2009, Blood.

[11]  H. Kolb Graft-versus-leukemia effects of transplantation and donor lymphocytes. , 2008, Blood.

[12]  A. Barrett Understanding and harnessing the graft‐versus‐leukaemia effect , 2008, British journal of haematology.

[13]  W. Leisenring,et al.  An acute graft-versus-host disease activity index to predict survival after hematopoietic cell transplantation with myeloablative conditioning regimens. , 2006, Blood.

[14]  M. Sorror,et al.  Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  M. Turner,et al.  National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. , 2005, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[16]  R. Storb,et al.  Duration of immunosuppressive treatment for chronic graft-versus-host disease. , 2004, Blood.

[17]  M. Sorror,et al.  Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning , 2004 .

[18]  H. Deeg,et al.  Increasingly frequent diagnosis of acute gastrointestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation. , 2004, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[19]  K. Ishiyama,et al.  Graft-versus-leukemia effect of allogeneic stem cell transplantation; a Japanese single center study. , 2004, Haematologica.

[20]  S. Iacobelli,et al.  Graft-versus-host disease and outcome in HLA-identical sibling transplantations for chronic myeloid leukemia. , 2002, Blood.

[21]  Katia Perruccio,et al.  Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic Transplants , 2002, Science.

[22]  F. Appelbaum,et al.  Haematopoietic cell transplantation as immunotherapy , 2001, Nature.

[23]  E. Elonen,et al.  Cyclosporine, methotrexate, and methylprednisolone compared with cyclosporine and methotrexate for the prevention of graft-versus-host disease in bone marrow transplantation from HLA-identical sibling donor: a prospective randomized study. , 2000, Blood.

[24]  G. Dini,et al.  Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA-identical sibling bone marrow transplantation: results of a randomized trial. , 2000, Blood.

[25]  J. V. Stone,et al.  Long-Term Survival and Late Deaths after Allogeneic Bone Marrow Transplantation , 1999 .

[26]  J. V. Stone,et al.  Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry. , 1999, The New England journal of medicine.

[27]  H. Deeg,et al.  Methotrexate and cyclosporine for graft-vs.-host disease prevention: what length of therapy with cyclosporine? , 1997, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[28]  Robert H. Collins,et al.  Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  A. Gratwohl,et al.  Acute graft-versus-host disease: grade and outcome in patients with chronic myelogenous leukemia. Working Party Chronic Leukemia of the European Group for Blood and Marrow Transplantation. , 1995, Blood.

[30]  H. Deeg,et al.  Effect of graft-versus-host disease prophylaxis on relapse in patients transplanted for acute myeloid leukemia. , 1994, Bone marrow transplantation.

[31]  A. Nademanee,et al.  Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prophylaxis of acute graft-versus-host disease. , 1993, The New England journal of medicine.

[32]  F. Frassoni,et al.  Increased risk of leukemia relapse with high-dose cyclosporine A after allogeneic marrow transplantation for acute leukemia. , 1991, Blood.

[33]  A. Rimm,et al.  Graft-versus-leukemia reactions after bone marrow transplantation. , 1990, Blood.

[34]  W. Wilmanns,et al.  Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. , 1990, Blood.

[35]  R Storb,et al.  Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. , 1989, Blood.

[36]  H. Deeg,et al.  Prednisone and Azathioprine Compared With Prednisone and Placebo for Treatment of Chronic Graft-v-Host Disease : Prognostic Influence of Prolonged Thrombocytopenia After Allogeneic Marrow Transplantation , 2005 .

[37]  K. Sullivan,et al.  Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. , 1981, The New England journal of medicine.

[38]  R. Storb,et al.  Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. , 1979, The New England journal of medicine.